Psychological stress in adolescent and adult mice increases neuroinflammation and attenuates the response to LPS challenge

• Type of Material: Article
• Authors: Christopher J. Barnum, Emory University; Thaddeus Pace, Emory University; Fang Hua, Emory University; Gretchen Neigh, Emory University; Malu Tansey, Emory University
• Language: English
• Date: 2012-01-16
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2012 Barnum et al; licensee BioMed Central Ltd.
• License: Creative Commons Attribution 2.0 Generic
• Final Published Version (URL): http://www.jneuroinflammation.com/content/9/1/9
• Title of Journal or Parent Work: Journal of Neuroinflammation
• ISSN: 1742-2094
• Volume: 9
• Issue: 9
• Start Page: 1
• End Page: 15
• Grant/Funding Information: This work was supported by the NIH/NINDS institutional training grant Training in translational research in Neurology (T32NS007480, CJB), the Michael J. Fox Foundation for Parkinson's Research (CJB), the National Institutes of Health grants 2R01NS049433 (MGT), and 5R21MH85210 (TWWP).
• Research Categories: Biology, Neuroscience

Abstract

Background There is ample evidence that psychological stress adversely affects many diseases. Recent evidence has shown that intense stressors can increase inflammation within the brain, a known mediator of many diseases. However, long-term outcomes of chronic psychological stressors that elicit a neuroinflammatory response remain unknown. Methods To address this, we have modified previously described models of rat/mouse predatory stress (PS) to increase the intensity of the interaction. We postulated that these modifications would enhance the predator-prey experience and increase neuroinflammation and behavioral dysfunction in prey animals. In addition, another group of mice were subjected to a modified version of chronic unpredictable stress (CUS), an often-used model of chronic stress that utilizes a combination of stressors that include physical, psychological, chemical, and other. The CUS model has been shown to exacerbate a number of inflammatory-related diseases via an unknown mechanism. Using these two models we sought to determine: 1) whether chronic PS or CUS modulated the inflammatory response as a proposed mechanism by which behavioral deficits might be mediated, and 2) whether chronic exposure to a pure psychological stressor (PS) leads to deficits similar to those produced by a CUS model containing psychological and physical stressors. Finally, to determine whether acute PS has neuroinflammatory consequences, adult mice were examined at various time-points after PS for changes in inflammation. Results Adolescent mice subjected to chronic PS had increased basal expression of inflammation within the midbrain. CUS and chronic PS mice also had an impaired inflammatory response to a subsequent lipopolysaccharide challenge and PS mice displayed increased anxiety- and depressive-like behaviors following chronic stress. Finally, adult mice subjected to acute predatory stress had increased gene expression of inflammatory factors. Conclusion Our results demonstrate that predatory stress, an ethologically relevant stressor, can elicit changes in neuroinflammation and behavior. The predatory stress model may be useful in elucidating mechanisms by which psychological stress modulates diseases with an inflammatory component.